Our primary research question was to determine if the optic nerve sheath diameter demonstrates a measurable change via ultrasound assessment in real time for patients undergoing elective lumbar punctures correlated with changes in intracranial pressure. This study was approved by the University of Pittsburgh institutional review board (PRO14040248). Study investigators obtained written informed consent from all patients (or guardians of participants) in the study prior to enrollment.
We conducted a prospective cohort convenience study. The participants were patients of a collaborating neurologist at the University of Pittsburgh Medical Center who were scheduled to receive diagnostic lumbar puncture. These patients represented a unique sample for assessing the dynamics of acute ICP changes. All measurements took place during scheduled out-patient lumbar puncture clinics at the office of this neurologist. Study team members had specific training on how to perform ONSD measurements with POCUS. The PI (CS) has extensive training in POCUS, particularly in regard to ONSD measurements. He directly taught and supervised the other team members (comprised an EM POCUS fellow, EM residents and a medical student research assistant) for hands-on training across several sessions as well as their initial patient enrollments to ensure accuracy of technique and measurements. Subsequent, unsupervised scans were reviewed for accuracy of the saved measurements.
We included adult patients, ages 18–89, undergoing a non-emergent, scheduled lumbar puncture for diagnostic indications. We excluded pregnant women, and patients with prosthetic eyes, cataracts, glaucoma, or recent eye trauma or surgery. Patient who received their LP sitting up were excluded as CSF pressure measurement in the sitting position is not known to be reliable.
We calculated sample size based on prior studies of the relationship between ONSD and ICP in human subjects. ONSD measurement has a median inter-observer variation of ± 0.2–0.3 mm [19]. In an intrathecal infusion test conducted in human subjects that induced raised ICP in subjects, the ONSD-to-ICP ratio varied from 0.019 to 0.071 mm/cm [16]. Choosing conservative values of an ONSD-to-ICP ratio of 0.025 mm/cm, and an ICP change of 10 cm, we calculated that we would need to enroll 17 patients with elevated ICP. With the addition of a 35% buffer for dropout (i.e., inability to complete LP or done while sitting up), this yielded an anticipated enrollment of 23 patients. However, as the investigators were blinded to these data, all consecutive patients meeting inclusion criteria had these measurements obtained. We planned to enroll consecutive patients until at least 17 patients with elevated ICP had been included. Anticipating that 20% of the patients will have high intracranial pressure (> 25 cm), we determined that the anticipated number to include would be 115.
After screening, enrolling and obtaining written informed consent, the study investigators performed ultrasound (US) measurements of the participants’ ONSD. All study team members were competent in the use of US to acquire these views and accurately obtain the ONSD measurements. The investigators used a GE vivid i ultrasound machine with an 8–16 MHz high-frequency linear probe (GE Healthcare, Chicago, IL, USA). ONSD measurements were obtained with the patient supine to correspond with opening pressure measurements of patients in the lateral decubitus position. Each subject received four pre-LP US ONSD measurements: both eyes were evaluated in the traverse and sagittal planes. Consistent with previously published studies, the width of the ONSD was measured at 3 mm behind the globe, in the axis perpendicular to the optic nerve, with the patient supine [20]. These images were saved as digital files, de-identified from any patient information, locally to the US device itself for subsequent quality assurance review of the images and accuracy of measurement by the senior members of the research team. At this time, the patient was taken for their scheduled LP.
The second set of measurements was performed after the patients’ LP. The research team member, blinded from the patients pre- and post-LP pressures and amount of cerebral spinal fluid (CSF) removed, performed repeat measurements from the both of the participant’s ONSD in transverse and sagittal plane. These images were also saved locally to the device. After the images were saved, the neurologist performing the LP provided the participant’s opening pressure, closing pressure and amount of CSF he removed. These results were entered into our database as well as the ONSD measurements pre- and post-LP. Opening pressure > 25 cm was used to categorize patients as having increased ICP. However, we included all patients to assess the changes in ONSD pre- and post-LP in those both with and without elevated ICP in order to better understand the elasticity on the ONSD in vivo.
Patient data were de-identified and blinded to the research team members performing the ONSD measurements. However, demographic information of the patients was collected, including indication for LP (i.e., presently ongoing or resolved symptoms) and other existing co-morbidities.
We used descriptive statistics to characterize the study subjects. We calculated average ONSD for each eye as the arithmetic mean of sagittal and transverse measurements. For each eye, we compared sagittal and transverse and average ONSD before and after LP using two-tailed paired t test. We calculated change in ONSD at each eye and axis from pre-LP to post-LP. We also examined LP opening pressure in the subset of subjects with abnormal ONSD (> 5 mm). We used linear regression to measure association of sagittal, transverse, average, and change in ONSD with LP opening pressure, change in LP pressure, and volume of CSF drained. We considered p values < 0.05 to be significant. We used STATA 14.2 for all analyses (STATA Corp., College Park, Tx).
Data Availability: Anonymized data not published within this article will be made available by request from any qualified investigator.
